DE19818485A1 - Reaction vessel, useful for diagnostic determination of diols such as catecholamines comprises a vessel coated with cis-diol affinity reagent - Google Patents
Reaction vessel, useful for diagnostic determination of diols such as catecholamines comprises a vessel coated with cis-diol affinity reagentInfo
- Publication number
- DE19818485A1 DE19818485A1 DE1998118485 DE19818485A DE19818485A1 DE 19818485 A1 DE19818485 A1 DE 19818485A1 DE 1998118485 DE1998118485 DE 1998118485 DE 19818485 A DE19818485 A DE 19818485A DE 19818485 A1 DE19818485 A1 DE 19818485A1
- Authority
- DE
- Germany
- Prior art keywords
- reaction vessel
- cis
- diol
- coated
- affinity medium
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000003943 catecholamines Chemical class 0.000 title description 4
- 150000002009 diols Chemical class 0.000 title description 3
- 239000003153 chemical reaction reagent Substances 0.000 title 1
- 238000000034 method Methods 0.000 claims description 16
- 238000010438 heat treatment Methods 0.000 claims description 10
- 239000000126 substance Substances 0.000 claims description 10
- 238000000605 extraction Methods 0.000 claims description 7
- 239000011159 matrix material Substances 0.000 claims description 6
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 5
- 239000000872 buffer Substances 0.000 claims description 5
- 229920002401 polyacrylamide Polymers 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000004793 Polystyrene Substances 0.000 claims description 2
- 229920002223 polystyrene Polymers 0.000 claims description 2
- 239000007788 liquid Substances 0.000 description 11
- 239000000203 mixture Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 238000003149 assay kit Methods 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- 239000012876 carrier material Substances 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000010792 warming Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 239000003570 air Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical class OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/22—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof comprising organic material
- B01J20/26—Synthetic macromolecular compounds
- B01J20/261—Synthetic macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/28—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties
- B01J20/28014—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof characterised by their form or physical properties characterised by their form
- B01J20/28047—Gels
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/3078—Thermal treatment, e.g. calcining or pyrolizing
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3202—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the carrier, support or substrate used for impregnation or coating
- B01J20/3206—Organic carriers, supports or substrates
- B01J20/3208—Polymeric carriers, supports or substrates
- B01J20/321—Polymeric carriers, supports or substrates consisting of a polymer obtained by reactions involving only carbon to carbon unsaturated bonds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
- B01J20/30—Processes for preparing, regenerating, or reactivating
- B01J20/32—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating
- B01J20/3231—Impregnating or coating ; Solid sorbent compositions obtained from processes involving impregnating or coating characterised by the coating or impregnating layer
- B01J20/3242—Layers with a functional group, e.g. an affinity material, a ligand, a reactant or a complexing group
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/40—Concentrating samples
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/54353—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals with ligand attached to the carrier via a chemical coupling agent
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
- G01N33/544—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being organic
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/94—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors
- G01N33/9406—Neurotransmitters
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2220/00—Aspects relating to sorbent materials
- B01J2220/50—Aspects relating to the use of sorbent or filter aid materials
- B01J2220/66—Other type of housings or containers not covered by B01J2220/58 - B01J2220/64
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Organic Chemistry (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- General Health & Medical Sciences (AREA)
- Pathology (AREA)
- General Physics & Mathematics (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Medicinal Chemistry (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Biotechnology (AREA)
- Thermal Sciences (AREA)
- Dispersion Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Apparatus Associated With Microorganisms And Enzymes (AREA)
Abstract
Description
Die vorliegende Erfindung betrifft Reaktionsgefäße, deren Oberfläche mit einem cis-Diol-spezifischen Affinitätsmedium beschichtet ist, sowie Verfahren zu deren Herstellung und Testbestecke enthaltend derartige Reaktionsgefäße.The present invention relates to reaction vessels, the Surface with a cis-diol specific affinity medium is coated, and processes for their preparation and Test kits containing such test tubes.
Auf dem Gebiet der medizinischen Diagnostik besteht grund sätzlich das Bestreben, für die verschiedensten nachzuwei senden Substanzen kostengünstige, einfach zu handhabende, präzise und schnelle Nachweisverfahren und entsprechende Testbestecke zur Verfügung zu stellen. Ein wichtiges Feld stellt dabei im Rahmen der Diagnostik der Nachweis von Ka techolaminen, wie z. B. Adrenalin, Noradrenalin oder Dopamin, in Proben von Körperflüssigkeiten dar. Ein erster wichtiger Schritt bei diesen Nachweisverfahren ist die Extraktion der Katecholamine aus der jeweiligen Probe. Herkömmlicherweise werden für diese Extraktion, die eine wesentliche Reinigung und gleichzeitig eine Aufkonzentrierung bewirkt, Substanzen als Affinitätsliganden verwendet, welche die cis-Diol-Struk turen der Katecholamine erkennen, z. B. immobilisierte Bor säure oder Borsäurederivate (siehe z. B. Speek et al., Clinica Chimica Acta 128 (1983), 103-113 oder Gelijkens und De Leenheer, Journal of Chromatography 183 (1980), 78-82) oder Aluminiumoxid (siehe z. B. Cooper et al., Journal of Neuroscience Methods 22 (1987), 31-39 oder Refshauge et al., Life Sciences 14 (1974), 311-322). Gewöhnlicherweise wird dabei zur Extraktion die entsprechende Probe mit einem Affi nitätsmedium in Suspension gemischt, wobei sich das Medium auch in einer Chromatographiesäule oder einem anderen Gefäß befinden kann. Nach Waschen des Affinitätsmediums werden die daran gebundenen Substanzen wieder abgetrennt (siehe z. B. Mazzeo und Krull, Biochromatography 4 (1989), 124-130 und Hageman und Kuehn, Methods in Biology 11: Practical Protein Chromatography, Ed. Kennedy und Fowell, The Humana Press Inc. (1992), 45-71). Diese Vorgänge, die mehrere Zentrifuga tions-, Pipettierungs- bzw. Waschschritte umfassen, stellen eine erhebliche Fehlerquelle bei der präzisen Bestimmung der Konzentration der nachzuweisenden Substanz dar und sind dar über hinaus zeitintensiv.There is reason in the field of medical diagnostics In addition, the endeavor to prove for the most varied send substances inexpensive, easy to use, precise and fast detection procedures and corresponding To provide test kits. An important field provides proof of Ka in the context of diagnostics techolamines such as B. adrenaline, noradrenaline or dopamine, in samples of body fluids. A first important one The step in this detection procedure is the extraction of the Catecholamines from the respective sample. Traditionally are for this extraction, which is an essential cleaning and at the same time causes concentration, substances used as affinity ligands, which the cis-diol structure recognize doors of the catecholamines, e.g. B. immobilized boron acid or boric acid derivatives (see e.g. Speek et al., Clinica Chimica Acta 128 (1983), 103-113 or Gelijkens and De Leenheer, Journal of Chromatography 183 (1980), 78-82) or alumina (see, e.g., Cooper et al., Journal of Neuroscience Methods 22 (1987), 31-39 or Refshauge et al., Life Sciences 14: 311-322 (1974). Usually it will extract the corresponding sample with an affi nitätsmedium mixed in suspension, the medium also in a chromatography column or another vessel can be located. After washing the affinity medium, the substances bound to it are separated again (see e.g. Mazzeo and Krull, Biochromatography 4 (1989), 124-130 and Hageman and Kuehn, Methods in Biology 11: Practical Protein Chromatography, Ed. Kennedy and Fowell, The Humana Press Inc. (1992), 45-71). These processes, the multiple centrifuga tion, pipetting or washing steps a significant source of error in the precise determination of the Concentration of the substance to be detected and are moreover time consuming.
Der vorliegenden Anmeldung liegt somit die Aufgabe zugrunde, Mittel zur Verfügung zu stellen, die die Extraktion von nachzuweisenden Substanzen aus Proben vereinfachen.The present application is therefore based on the task To provide funds for the extraction of Simplify substances to be detected from samples.
Diese Aufgabe wird erfindungsgemäß durch die Bereitstellung der in den Patentansprüchen bezeichneten Ausführungsformen gelöst.This object is achieved by the provision of the embodiments described in the claims solved.
Somit betrifft die vorliegende Erfindung ein Reaktionsgefäß, dessen Oberfläche beschichtet ist mit einem cis-Diol-spezi fischen Affinitätsmedium. The present invention thus relates to a reaction vessel whose surface is coated with a cis-diol special fish affinity medium.
Derartige Reaktionsgefäße erlauben es nun, den Extraktions schritt beim Nachweis von Substanzen mit cis-Diol-Struktur, wie z. B. Polyphenolen (z. B. Katecholaminen und Flavonoiden), 1,2-Hydroxysäuren, 1,2-Hydroxylaminen, Enzymen (z. B. Serin- Proteinasen) und anderen Proteinen (z. B. Albumin), Nuclein säuren (z. B. Nucleosiden, Nucleotiden und RNA's), Kohlen hydraten (z. B. Glucose) und anderen Verbindungen, die Koh lenhydrat-Strukturen enthalten, schneller und präziser durchzuführen. Unter Verwendung der erfindungsgemäßen Reak tionsgefäße entfallen bei dem Extraktionsschritt alle Zen trifugationsschritte und die Pipettierungsschritte werden reduziert. Die Trennung der flüssigen von der festen Phase erfolgt in diesem Fall durch Dekantieren und Ausklopfen der Reaktionsgefäße auf einer saugfähigen Unterlage.Such reaction vessels now allow extraction step in the detection of substances with a cis-diol structure, such as B. polyphenols (e.g. catecholamines and flavonoids), 1,2-hydroxy acids, 1,2-hydroxylamines, enzymes (e.g. serine Proteinases) and other proteins (e.g. albumin), nuclein acids (e.g. nucleosides, nucleotides and RNA's), coals hydrates (e.g. glucose) and other compounds that Koh Lenhydrate structures contain, faster and more precisely perform. Using the reak according to the invention In the extraction step, all vials are dispensed with centrifugation steps and the pipetting steps reduced. The separation of the liquid from the solid phase is done in this case by decanting and tapping the Reaction tubes on an absorbent pad.
Der Begriff "Reaktionsgefäß" umfaßt im Zusammenhang mit der vorliegenden Erfindung jede Art von herkömmlicherweise in der Diagnostik verwendeten Gefäßen, die zur Aufnahme einer Probe, insbesondere in flüssiger Form geeignet sind. Hierzu zählen beispielsweise jede Art von Zentrifugenröhrchen, Makro- oder Mikrotiterplatten, Multischalen, Zell- oder Ge webekulturplatten oder -schalen, Röhrchen, Flaschen oder Wannen. Das Volumen dieser Gefäße spielt dabei keine Rolle. Es liegt vorzugsweise in einem Bereich von 5 µl bis 100 ml, besonders bevorzugt in einem Bereich von 500 µl bis 5 ml und insbesondere in einem Bereich von 1,5 ml bis 2,5 ml. Die Re aktionsgefäße sollten vorzugsweise aus Kunststoff sein. Be vorzugt bestehen sie ganz oder teilweise aus Polystyrol.The term "reaction vessel" in connection with the present invention any type of conventionally in used in the diagnostics to hold a Sample, especially in liquid form are suitable. For this count any kind of centrifuge tube, Macro or microtiter plates, multi-wells, cell or Ge weave culture plates or dishes, tubes, bottles or Tubs. The volume of these vessels is irrelevant. It is preferably in a range from 5 μl to 100 ml, particularly preferably in a range from 500 μl to 5 ml and especially in a range from 1.5 ml to 2.5 ml. The Re Action vessels should preferably be made of plastic. Be preferably they consist entirely or partially of polystyrene.
Der Ausdruck "dessen Oberfläche beschichtet ist" bedeutet, daß zumindest der Großteil derjenigen Oberfläche, die mit der zu untersuchenden Probe in Kontakt kommt, mit dem cis- Diol-spezifischen Affinitätsmedium beschichtet ist. "Be schichtet" bedeutet dabei, daß das Affinitätsmedium die Oberfläche des Reaktionsgefäßes überzieht und sich bei Kon takt mit der zu untersuchenden Probe nicht von dieser löst. The expression "whose surface is coated" means that at least the majority of the surface that with the sample to be examined comes into contact with the cis- Diol-specific affinity medium is coated. "Be stratifies "means that the affinity medium The surface of the reaction vessel is coated and at Kon does not detach from the sample to be examined.
Unter dem Begriff "cis-Diol-spezifisches Affinitätsmedium" wird im Rahmen der vorliegenden Erfindung ein Material ver standen, das aus einem Trägermaterial (Matrix) besteht; wel ches chemische Strukturen (Liganden) aufweist, die spezi fisch Substanzen mit einer cis-Diol-Struktur binden können. Das Trägermaterial ist dabei vorzugsweise ein Material wie es für die Herstellung von Chromatographie-Trennmedien ver wendet wird.Under the term "cis-diol-specific affinity medium" a material is ver within the scope of the present invention stood, which consists of a carrier material (matrix); wel ches chemical structures (ligands), the speci fish can bind substances with a cis-diol structure. The carrier material is preferably a material such as it for the production of chromatography separation media is applied.
In einer bevorzugten Ausführungsform ist die Matrix des cis- Diol-spezifischen Affinitätsmediums Polyacrylamid.In a preferred embodiment, the matrix of the cis- Diol-specific affinity medium polyacrylamide.
In einer besonders bevorzugten Ausführungsform ist das cis- Diol-spezifische Affinitätsmedium ein Boronat-Affinitätsgel. Ein derartiges Gel ist kommerziell erhältlich, z. B. unter der Bezeichnung Affi-Gel 601 (Firma BIO-RAD, Katalognr. 153-6101 und 153-6102).In a particularly preferred embodiment, the cis Diol-specific affinity medium is a boronate affinity gel. Such a gel is commercially available, e.g. More colorful the name Affi-Gel 601 (company BIO-RAD, catalog No. 153-6101 and 153-6102).
Ferner betrifft die vorliegende Erfindung ein Verfahren zur
Herstellung eines erfindungsgemäßen Reaktionsgefäßes umfas
send die folgenden Schritte:
The present invention further relates to a method for producing a reaction vessel according to the invention, comprising the following steps:
- a) Inkontaktbringen des cis-Diol-spezifischen Affinitätsme diums mit der inneren Oberfläche des zu beschichtenden Reaktionsgefäßes;a) Contacting the cis-diol-specific affinity measurement medium with the inner surface of the surface to be coated Reaction vessel;
- b) Erwärmen des Reaktionsgefäßes; undb) heating the reaction vessel; and
- c) Abkühlen des Reaktionsgefäßes.c) cooling the reaction vessel.
Das Inkontaktbringen mit dem Reaktionsgefäß gemäß Schritt (a) des erfindungsgemäßen Verfahrens erfolgt vorzugsweise derart, daß eine angemessene Menge des cis-Diol-spezifischen Affinitätsmediums in das Reaktionsgefäß gebracht wird und dort für einen längeren Zeitraum verbleibt. "Angemessene Menge" bedeutet dabei eine Menge, die geeignet ist, die Oberfläche des Reaktionsgefäßes zum gewünschten Ausmaß zu bedecken.Contacting the reaction vessel according to step (a) The method according to the invention is preferably carried out such that an adequate amount of the cis-diol-specific Affinity medium is brought into the reaction vessel and stays there for a longer period of time. "Appropriate Quantity "means a quantity that is suitable, the Surface of the reaction vessel to the desired extent cover.
Das Inkontaktbringen nach Schritt (a) des Verfahrens kann sowohl derart erfolgen, daß das cis-Diol-spezifische Affini tätsmedium als solches direkt mit dem Reaktionsgefäß in Kon takt gebracht wird. Alternativ kann das Affinitätsmedium je doch auch mit anderen Feststoffen, z. B. anderen Affinitäts medien, Stabilisatoren, Füll- und Konservierungsstoffen, oder mit Gasen, z. B. Luft, Stickstoff oder Argon, gemischt werden und mit dem Reaktionsgefäß in Kontakt gebracht wer den. Vorzugsweise wird das cis-Diol-spezifische Affinitäts medium vor dem Inkontaktbringen mit dem Reaktionsgefäß mit einer Flüssigkeit gemischt und das Gemisch aus Affinitätsme dium und Flüssigkeit wird in das Reaktionsgefäß eingebracht. Das Mischen erfolgt dabei vorzugsweise derart, daß das cis- Diol-spezifische Affinitätsmedium unter ständigem Rühren zu einer Flüssigkeit gegeben wird. Das entstandene Gemisch wird dann vorzugsweise für längere Zeit, insbesondere für ca. 30 Minuten, weiter gerührt bis das Affinitätsmedium gut aufge schlämmt ist und eine optisch homogene, fein verteilte Mi schung des Affinitätsmediums in der Flüssigkeit vorliegt.The contacting after step (a) of the method can both be done in such a way that the cis-diol-specific affini Act medium as such directly with the reaction vessel in Kon clock is brought. Alternatively, the affinity medium can each but also with other solids, e.g. B. other affinity media, stabilizers, fillers and preservatives, or with gases, e.g. As air, nitrogen or argon, mixed and who are brought into contact with the reaction vessel the. Preferably the cis-diol specific affinity medium before contacting the reaction vessel mixed with a liquid and the mixture from Affinitätsme Medium and liquid are introduced into the reaction vessel. The mixing is preferably carried out in such a way that the cis Diol-specific affinity medium with constant stirring is given to a liquid. The resulting mixture is then preferably for a long time, especially for about 30 Minutes, continue stirring until the affinity medium is well applied is slurried and an optically homogeneous, finely divided Mi the affinity medium is present in the liquid.
Flüssigkeiten, die in diesem Zusammenhang verwendet werden können, sind beispielsweise wäßrige Lösungen (z. B. Puffer), organische Lösungsmittel (z. B. Kohlenwasserstoffe, Alkohole, Ether), Säuren und Laugen. Bei der Flüssigkeit handelt es sich vorzugsweise um Reinstwasser.Liquids used in this context are, for example, aqueous solutions (e.g. buffers), organic solvents (e.g. hydrocarbons, alcohols, Ether), acids and alkalis. It's about the liquid preferably pure water.
Wird das Affinitätsmedium mit einer Flüssigkeit gemischt, so wird nach Schritt (a) ein Trocknungsschritt durchgeführt, der gewährleistet, daß in dem Gemisch vorhandene Flüssigkeit weitgehend, vorzugsweise bis zu einer Restfeuchte von weni ger als 1% und besonders bevorzugt vollständig entfernt wird. Besonders bevorzugt wird das Trocknenlassen des in das Reaktionsgefäß eingebrachten Gemisches aus cis-Diol-spezifi schem Affinitätsgel und einer Flüssigkeit derart durchge führt, daß das mit dem Gemisch versehene Reaktionsgefäß über einen längeren Zeitraum, vorzugsweise für 5 Minuten bis 5 Stunden bei einer Temperatur zwischen 4°C und 30°C aufbe wahrt wird.If the affinity medium is mixed with a liquid, then a drying step is carried out after step (a), which ensures that liquid present in the mixture largely, preferably up to a residual moisture of few less than 1% and particularly preferably completely removed becomes. It is particularly preferred to let the dry in the Mixture of cis-diol-specific introduced into the reaction vessel so-called affinity gel and a liquid leads that the reaction vessel provided with the mixture over a longer period, preferably for 5 minutes to 5 Hours at a temperature between 4 ° C and 30 ° C is preserved.
Die Höhe der Temperatur sowie die Dauer der Erwärmung gemäß Schritt (b) des erfindungsgemäßen Verfahrens richtet sich gegebenenfalls nach dem Material des zu beschichtenden Reak tionsgefäßes sowie nach der Art der Matrix des Affinitätsme diums. Die Parameter können jedoch durch den Fachmann durch geeignete Versuche problemlos eingestellt werden.The amount of temperature as well as the duration of heating according to Step (b) of the method according to the invention is directed if necessary, according to the material of the reak to be coated tion vessel and according to the type of matrix of the Affinitätsme diums. However, the parameters can be determined by the person skilled in the art suitable trials can be set easily.
Eine "Erwärmung" bedeutet im Rahmen der vorliegenden Erfin dung vorzugsweise eine Erwärmung auf eine Temperatur von mindestens 50°C, bevorzugt von mindestens 60°C, und beson ders bevorzugt von mindestens 70°C. Ferner bedeutet eine Er wärmung vorzugsweise eine Erwärmung auf nicht mehr als 100°C, bevorzugt auf nicht mehr als 90°C. Eine Erwärmung im Bereich von 70°C bis 90°C ist besonders bevorzugt. Die Dauer der Erwärmung beträgt vorzugsweise mindestens 30 min. bevor zugt mindestens 60 min und besonders bevorzugt mindestens 120 min. Die Dauer übersteigt vorzugsweise nicht 360 min. bevorzugt nicht 300 min und besonders bevorzugt nicht 240 min. Ganz besonders bevorzugt erfolgt die Erwärmung für 1 bis 5 Stunden.In the context of the present invention, "warming" means preferably heating to a temperature of at least 50 ° C, preferably at least 60 ° C, and esp preferably at least 70 ° C. Furthermore, an He means heating preferably a heating to no more than 100 ° C, preferably not more than 90 ° C. A warming in the The range of 70 ° C to 90 ° C is particularly preferred. The duration the heating is preferably at least 30 minutes. before draws at least 60 min and particularly preferably at least 120 min. The duration preferably does not exceed 360 minutes. preferably not 300 min and particularly preferably not 240 min. The heating is very particularly preferably carried out for 1 up to 5 hours.
Das Abkühlen des beschichteten Reaktionsgefäßes gemäß Schritt (c) des erfindungsgemäßen Verfahrens erfolgt vor zugsweise durch Stehenlassen bei Raumtemperatur.The cooling of the coated reaction vessel according to Step (c) of the method according to the invention takes place before preferably by standing at room temperature.
Im Zusammenhang mit dem Verfahren trifft für das Reaktions gefäß und das cis-Diol-spezifische Affinitätsmedium dasselbe zu wie bereits weiter oben erläutert.In connection with the procedure hits for the reaction vessel and the cis-diol specific affinity medium the same to as already explained above.
In einer bevorzugten Ausführungsform ist das zur Beschich tung mittels des erfindungsgemäßen Verfahrens verwendete cis-Diol-spezifische Affinitätsmedium ein Boronat-Affini tätsgel.In a preferred embodiment, this is for coating device used by the method according to the invention cis-diol-specific affinity medium a boronate affini murder gel.
In einer weiteren bevorzugten Ausführungsform ist die Matrix des cis-Diol-spezifischen Affinitätsmediums Polyacrylamid.In a further preferred embodiment, the matrix is of the cis-diol-specific affinity medium polyacrylamide.
Die vorliegende Erfindung betrifft ebenfalls Reaktionsgefäße die erhältlich sind durch das erfindungsgemäße Verfahren. The present invention also relates to reaction vessels which are obtainable by the process according to the invention.
Ferner betrifft die vorliegende Erfindung auch Testbestecke, insbesondere solche für diagnostische Zwecke, enthaltend ein erfindungsgemäßes Reaktionsgefäß.Furthermore, the present invention also relates to test kits, in particular those for diagnostic purposes, containing a reaction vessel according to the invention.
In einer bevorzugten Ausführungsform enthält ein erfindungs gemäßes Testbesteck auch Puffer zur Extraktion von Substan zen mit cis-Diol-Struktur, die an die Beschichtung des er findungsgemäßen Reaktionsgefäßes binden. Darunter fallen beispielsweise Acetat-, Borat-, Carbonat-, Citrat- und Phos phat-Puffer sowie Puffer basischer Amine (z. B. Tris-, Etha nolamin- und HEPES-Puffer).In a preferred embodiment contains a fiction appropriate test kit also buffers for extraction of substance zen with cis-diol structure attached to the coating of the er bind the reaction vessel according to the invention. This includes for example acetate, borate, carbonate, citrate and phos phat buffers and buffers of basic amines (e.g. Tris, Etha nolamine and HEPES buffers).
Das folgende Beispiel dient der näheren Erläuterung der Er findung.The following example is used to explain the Er finding.
Auf der Präzisionswaage werden 28,8 g Affi-Gel 601 (Fa. Bio- Rad) ausgewogen. Das Gel wird unter Rühren zu 1200 ml Reinstwasser gegeben. Das Rühren mit Hilfe eines Magnetrüh rers wird für 30 Minuten bei Raumtemperatur fortgesetzt. Die homogene Mischung wird für die Beschichtung von Makrotiter platten (Fa. NUNC) weiterhin gerührt.28.8 g Affi-Gel 601 (from Bio- Wheel) balanced. The gel becomes 1200 ml with stirring Given ultrapure water. Stirring using a magnetic stirrer rers is continued for 30 minutes at room temperature. The homogeneous mixture is used for the coating of macrotiter plates (NUNC) continued to stir.
Zur Beschichtung dieser Platten wird eine Pipette (Fa. Eppendorf) verwendet. Pro Vertiefung der Makrotiterplatte werden 250 µl des Gel-/Wasser-Gemisches pipettiert. Der Combitip sollte vor und zwischen den Pipettiergängen immer wieder aufgezogen und ausgestoßen werden. Das Gel sollte sich nach dem Pipettieren gleichmäßig auf dem Boden jeder Vertiefung verteilen.A pipette (Fa. Eppendorf) used. Per well of the macrotiter plate 250 ul of the gel / water mixture are pipetted. The Combitip should always be before and between pipetting be raised and expelled again. The gel should themselves evenly on the floor after pipetting Distribute deepening.
Die Makrotiterplatten mit dem eingebrachten Gel-/Wasser-Ge misch werden für 48 Stunden unter dem Abzug durch Abdampfen des Wassers bei Raumtemperatur getrocknet. The macrotiter plates with the introduced gel / water Ge mix for 48 hours under the hood by evaporation of the water dried at room temperature.
Die getrockneten Makrotiterplatten werden in einem Trocken schrank (VTR 5050, Fa. Heraeus Instruments) gestapelt und innerhalb von 2 Stunden auf eine Temperatur von 80°C er wärmt. Unter Aufrechterhaltung dieser Temperatur von 80°C wird das Erwärmen für weitere 2 Stunden fortgesetzt. An schließend werden die Makrotiterplatten aus dem Wärmeschrank entnommen und durch Stehenlassen für 2 Stunden bei Raumtem peratur abgekühlt.The dried macrotiter plates are in a dry cabinet (VTR 5050, Heraeus Instruments) stacked and within 2 hours to a temperature of 80 ° C warms. Maintaining this temperature of 80 ° C heating is continued for another 2 hours. On the macrotiter plates are then removed from the heating cabinet removed and left standing for 2 hours at room temperature temperature cooled.
Claims (11)
- a) Inkontaktbringen des cis-Diol-spezifischen Affini tätsmediums mit der inneren Oberfläche des zu be schichtenden Reaktionsgefäßes;
- b) Erwärmen des Reaktionsgefäßes; und
- c) Abkühlen des Reaktionsgefäßes.
- a) bringing the cis-diol-specific affinity medium into contact with the inner surface of the reaction vessel to be coated;
- b) heating the reaction vessel; and
- c) cooling the reaction vessel.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE1998118485 DE19818485B4 (en) | 1998-04-24 | 1998-04-24 | Reaction vessels coated with a cis-diol-specific affinity medium, as well as processes for their preparation |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE1998118485 DE19818485B4 (en) | 1998-04-24 | 1998-04-24 | Reaction vessels coated with a cis-diol-specific affinity medium, as well as processes for their preparation |
Publications (2)
Publication Number | Publication Date |
---|---|
DE19818485A1 true DE19818485A1 (en) | 2001-08-09 |
DE19818485B4 DE19818485B4 (en) | 2005-03-24 |
Family
ID=7865751
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
DE1998118485 Expired - Lifetime DE19818485B4 (en) | 1998-04-24 | 1998-04-24 | Reaction vessels coated with a cis-diol-specific affinity medium, as well as processes for their preparation |
Country Status (1)
Country | Link |
---|---|
DE (1) | DE19818485B4 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1835290A1 (en) * | 2006-03-17 | 2007-09-19 | Labor Diagnostika Nord GmbH & Co. KG | Assay for catecholamines |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102059103A (en) * | 2010-12-08 | 2011-05-18 | 南京大学 | Hydrophylic phenylboric acid functional porous integral material, preparation method and application thereof |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0389063A2 (en) * | 1989-03-23 | 1990-09-26 | Akzo Nobel N.V. | Process for isolating nucleic acid |
DE4420732A1 (en) * | 1994-06-15 | 1995-12-21 | Boehringer Mannheim Gmbh | Device for the treatment of nucleic acids from a sample |
DE19512361A1 (en) * | 1995-04-01 | 1996-10-02 | Boehringer Mannheim Gmbh | Method of isolating a biological material |
DE19512369A1 (en) * | 1995-04-01 | 1996-10-02 | Boehringer Mannheim Gmbh | Device for isolating nucleic acids |
US5565622A (en) * | 1994-09-15 | 1996-10-15 | Hewlett-Packard Co., Legal Dept. | Reduced solvent solid phase extraction |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1325980C (en) * | 1987-04-22 | 1994-01-11 | Sho Kikyotani | Apparatus for the treatment of biological samples and treatment methods using the same |
DE4310964A1 (en) * | 1992-04-16 | 1993-10-21 | Merck Patent Gmbh | Activated carrier materials, their preparation and use |
-
1998
- 1998-04-24 DE DE1998118485 patent/DE19818485B4/en not_active Expired - Lifetime
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0389063A2 (en) * | 1989-03-23 | 1990-09-26 | Akzo Nobel N.V. | Process for isolating nucleic acid |
DE4420732A1 (en) * | 1994-06-15 | 1995-12-21 | Boehringer Mannheim Gmbh | Device for the treatment of nucleic acids from a sample |
US5565622A (en) * | 1994-09-15 | 1996-10-15 | Hewlett-Packard Co., Legal Dept. | Reduced solvent solid phase extraction |
DE19512361A1 (en) * | 1995-04-01 | 1996-10-02 | Boehringer Mannheim Gmbh | Method of isolating a biological material |
DE19512369A1 (en) * | 1995-04-01 | 1996-10-02 | Boehringer Mannheim Gmbh | Device for isolating nucleic acids |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1835290A1 (en) * | 2006-03-17 | 2007-09-19 | Labor Diagnostika Nord GmbH & Co. KG | Assay for catecholamines |
Also Published As
Publication number | Publication date |
---|---|
DE19818485B4 (en) | 2005-03-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5118428A (en) | Method to remove red blood cells from whole blood samples | |
DE60024448T2 (en) | SYSTEM FOR ELECTROCHEMICAL QUANTITATIVE ANALYSIS OF ANALYZES IN A SOLID PHASE | |
DE60031357T2 (en) | Devices, kits and methods for testing body fluids for screening newborns by tandem mass spectrometry kits | |
Chen et al. | Application of probe electrospray to direct ambient analysis of biological samples | |
US6258531B1 (en) | Method of isolating a biological material | |
CN108499549A (en) | Solid phase micro-extracting head and preparation method thereof for being enriched with perfluorochemical | |
Xue et al. | Determination of lactate dehydrogenase isoenzymes in single lymphocytes from normal and leukemia cell lines | |
DE112014001433T5 (en) | Method for determining derivatized analytes in a separated biological fluid | |
Wernly et al. | Confirmation testing of 11-nor-Δ9-tetrahydrocannabinol-9-carboxylic acid in urine with micellar electrokinetic capillary chromatography | |
Okeyo et al. | Analysis of estrogens and anabolic steroids by SPME with on‐fiber derivatization and GC/MS | |
DE19818485A1 (en) | Reaction vessel, useful for diagnostic determination of diols such as catecholamines comprises a vessel coated with cis-diol affinity reagent | |
DE4124778A1 (en) | METHOD AND ARRANGEMENT FOR ANALYZING AGGLUTINATION REACTIONS | |
DE60100025T2 (en) | Treatment of proteins from gels for analysis using mass spectrometry | |
US20040147040A1 (en) | Multidimensional separation of biosubstance mixtures for mass spectrometric analysis | |
DE4038899C2 (en) | Methods and reagents for the determination of the enzymatic activity of transglutaminases (EC 2.3.2.13) | |
DE19962577A1 (en) | Chromatography material and method using the same | |
EP2411811B1 (en) | Layering for separating particles | |
WO2022232506A1 (en) | Biological sample capture with multiplex analysis | |
WO2000008511A1 (en) | Slides with reaction zones defined by hydrophobic barriers | |
Reyes-Garcés | Solid Phase Microextraction as a Sample Preparation Tool for Targeted and Untargeted Analysis of Biological Matrices | |
WO1990004038A1 (en) | Process for determining the activity of transglutaminases | |
AT524623B1 (en) | Solid support comprising a set of protein arrays | |
Bladek et al. | Application of Thin‐Layer Chromatography in Clinical Chemistry | |
DE3045199A1 (en) | Solid-phase immunoassay method - using reagent plate with perforated wells fitting into wells in sample plate | |
DE19617731B4 (en) | Method and device for determining the activity of enzymes and concentration of inhibitors in liquids |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
OP8 | Request for examination as to paragraph 44 patent law | ||
8181 | Inventor (new situation) |
Inventor name: WESTERMANN, JUERGEN, 21360 VUEGELSEN, DE |
|
8364 | No opposition during term of opposition | ||
R071 | Expiry of right |